The field of the invention concerns new protected amino acid derivatives useful for peptide synthesis, namely, N.sub..alpha. -2-(4-nitrophenylsulfonyl)ethoxycarbonyl-amino acids having the general formula I: ##STR2##
wherein R.sub.1 represents a hydrogen atom, and R.sub.2 may represent hydroxymethyl, 1-hydroxyethyl, 4-hydroxybenzyl, imidazolyl-2-methyl, benzyloxymethyl, 1-benzyloxyethyl, 4-benzyloxybenzyl, benzyloxycarbonylmethyl, 2-(benzyloxycarbonyl)ethyl, S-benzylthiomethyl, S-(diphenylmethyl)thiomethyl, 4-(benzyloxycarbamido)butyl, 3-guanidinopropyl, 3-N.sup.G -toluenesulfonyl) guanidinopropyl, 3-(N.sup.G -nitro) guanidinopropyl, 3-[N.sup.G -(4-methoxy-2,3,6-trimethylbenzenesulfonyl)]-guanidinopropyl, N-(4,4'-dimethoxybenzhydryl)carboxamidomethyl, 2-[N-(4,4'-dimethoxybenzhydryl) carboxamido]ethyl, S-tert-butyldithiomethyl, 4-[2-(4-nitrophenylsulfonyl)ethoxycarbamicdo]-butyl, propyl, butyl, ethyl, 3-(benzyloxycarbamido)propyl, or 3-(tert-butoxycarbamido)propyl, and methods for the preparation thereof.
N.sub.60 -2-(4-Nitrophenylsulfonyl) ethoxycarbonyl-amino acids (Nsc-amino acids) I represent a class of protected amino acid derivatives which are used in the chemical synthesis of peptides. In these derivatives, N.sub..alpha. -2-(4-nitrophenylsulfonyl) -ethoxycarbonyl (Nsc) group serves as a temporary N.sub..alpha. -protection which can be selectively removed after each step of the peptide chain elongation. Nsc-Group is fairly resistant to acidic reagents and is cleaved according to the .beta.-elimination mechanism by organic bases in aprotic solvents. Mild conditions of the cleavage allow for use of the temporary N.sub..alpha. -Nsc-protection in the peptide synthesis together with the acid-sensitive side chain protection of widely used t-butyl or benzyl type, thus providing the so-called "orthogonality" of the synthetic strategy.
Recently N.sub..alpha. -Nsc-amino acids, methods for their preparation, and their employment for the solid phase peptids synthesis have been disclosed in International Publication No. WO96/25394. However, only a minimal set of N.sub..alpha. -Nsc-derivatives of proteogenic amino acids has been described, which is intended for the solid phase peptide synthesis with full side-chain protection of acid-labile tert-butyl or compatible type.